Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma

Y. Hayami, S. Iida, N. Nakazawa, I. Hanamura, M. Kato, H. Komatsu, I. Miura, Bhavana J Dave, W. G. Sanger, B. Lim, M. Taniwaki, R. Ueda

Research output: Contribution to journalArticle

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Abstract

Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sγ3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosome-associated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.

Original languageEnglish (US)
Pages (from-to)1650-1657
Number of pages8
JournalLeukemia
Volume17
Issue number8
DOIs
StatePublished - Aug 1 2003

Fingerprint

Gene Rearrangement
DNA Methylation
Lysosomes
Multiple Myeloma
Introns
Cell Line
Alleles
Tretinoin
Proteins
Immunoglobulin Heavy Chain Genes
Genetic Translocation
Cell Lineage
Plasma Cells
Genes
B-Lymphocytes
Gene Expression
Messenger RNA
Neoplasms

Keywords

  • DNA methylation
  • E3/LAPTm5
  • Multiple myeloma
  • t(1;14)(p34; q32)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Hayami, Y., Iida, S., Nakazawa, N., Hanamura, I., Kato, M., Komatsu, H., ... Ueda, R. (2003). Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma. Leukemia, 17(8), 1650-1657. https://doi.org/10.1038/sj.leu.2403026

Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma. / Hayami, Y.; Iida, S.; Nakazawa, N.; Hanamura, I.; Kato, M.; Komatsu, H.; Miura, I.; Dave, Bhavana J; Sanger, W. G.; Lim, B.; Taniwaki, M.; Ueda, R.

In: Leukemia, Vol. 17, No. 8, 01.08.2003, p. 1650-1657.

Research output: Contribution to journalArticle

Hayami, Y, Iida, S, Nakazawa, N, Hanamura, I, Kato, M, Komatsu, H, Miura, I, Dave, BJ, Sanger, WG, Lim, B, Taniwaki, M & Ueda, R 2003, 'Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma', Leukemia, vol. 17, no. 8, pp. 1650-1657. https://doi.org/10.1038/sj.leu.2403026
Hayami, Y. ; Iida, S. ; Nakazawa, N. ; Hanamura, I. ; Kato, M. ; Komatsu, H. ; Miura, I. ; Dave, Bhavana J ; Sanger, W. G. ; Lim, B. ; Taniwaki, M. ; Ueda, R. / Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma. In: Leukemia. 2003 ; Vol. 17, No. 8. pp. 1650-1657.
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abstract = "Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sγ3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosome-associated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60{\%}) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.",
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AU - Iida, S.

AU - Nakazawa, N.

AU - Hanamura, I.

AU - Kato, M.

AU - Komatsu, H.

AU - Miura, I.

AU - Dave, Bhavana J

AU - Sanger, W. G.

AU - Lim, B.

AU - Taniwaki, M.

AU - Ueda, R.

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N2 - Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sγ3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosome-associated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.

AB - Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sγ3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosome-associated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.

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